Selective delivery molecules and methods of use
Disclosed herein is a selective delivery molecule comprising: (a) an acidic sequence (portion A) which is effective to inhibit or prevent the uptake into cells or tissue retention, (b) a molecular transport or retention sequence (portion B), and (c) a linker between portion A and portion B, and (d) at least one cargo moiety.
1. A peptide according to Peptide P-3:
2. A selective delivery molecule comprising a peptide according to Pentide P-3:
derivatized with a pair of acceptor and donor fluorescent moieties that are capable of undergoing Försters/fluorescence resonance energy transfer with the other.
3. The selective delivery molecule of claim 2 , wherein the acceptor fluorescent moiety is attached to one amino acid terminus of Peptide P-3 and the donor fluorescent moiety is attached to the opposite amino acid terminus of Peptide P-3.
4. The selective delivery molecule of claim 2 , wherein the acceptor and donor fluorescent moieties are selected from: Cy5 and Cy7, Cy5 and IRDye750, Cy5 and IRDye800, and Cy5 and ICG.
5. The selective delivery molecule of claim 2 , wherein the acceptor and donor fluorescent moieties are Cy5 and Cy7.
6. The selective delivery molecule of claim 5 , wherein Cy5 is conjugated to Peptide P-3 prior to conjugation of Cy7 to Peptide P-3.
7. The selective delivery molecule of claim 2 , wherein the selective delivery molecule has the formula of intermediate 9:
8. The selective delivery molecule of claim 2 , wherein the selective delivery molecule further comprises a PEG polymer.
9. The selective delivery molecule of claim 8 , wherein the PEG polymer has an average molecular weight of 500 Da, 2 kDa, 5 kDa, or 10 kDa.
10. The selective delivery molecule of claim 2 , wherein the selective delivery molecule is formulated with a pharmaceutically acceptable excipient.
11. The selective delivery molecule of claim 2 , wherein the selective delivery molecule is formulated for parenteral administration.
12. The selective delivery molecule of claim 2 , wherein the selective delivery molecule is formulated for intravenous, subcutaneous, intraperitoneal, intramuscular, intravascular, intrathecal, intravitreal, infusion, or local administration.
13. A method of visualizing a tissue of interest in an individual in need thereof, comprising:
i) administering to the individual a selective delivery molecule of claim 2 ; and
ii) visualizing at least one of the acceptor and donor fluorescent moieties.
14. The method of claim 13 , wherein the tissue of interest is cancerous tissue.
15. The method of claim 13 , wherein the tissue of interest is: breast cancer tissue, colorectal cancer tissue, squamous cell carcinoma tissue, skin cancer tissue, prostate cancer tissue, melanoma tissue, thyroid cancer tissue, ovarian cancer tissue, cancerous lymph node tissue, cervical cancer tissue, lung cancer tissue, pancreatic cancer tissue, head and neck cancer tissue, esophageal cancer tissue, or sarcoma.
16. The method of claim 13 , further comprising surgically removing the tissue of interest from the individual.
17. The method of claim 13 , wherein the surgical margin surrounding the tissue of interest is decreased.
18. The method of claim 13 , wherein the visualizing is used to guide surgery, to stage cancer tissue, to stage lymph nodes, or allows a surgeon to minimize the removal of healthy tissue.
19. A method of delivering a pair of acceptor and donor fluorescent moieties to a tissue of interest, comprising contacting the tissue of interest with a selective delivery molecule of claim 2 .
20. An excised tissue sample comprising:
a) an isolated tissue removed from a human body, and
b) a selective delivery molecule of claim 2 .